The long term objective of this proposal is to develop a commercial trivalent glycoprotein subunit vaccine for parainfluenza viruses. Because of the high cost of preparing these glycoproteins, ;a means for achieving an enhanced immune response is an important objective, and is the focus of this proposal. Biocompatible and biodegradable microspheres consisting of a copolymer of DL-lactide and glycolide (poly DL-lactide-co-glycolide) will be utilized to incorporate inactivated human parainfluenza type 3 (PI3) virus antigens into small spherical particles (1-10 um). Microspheres containing viral antigens will be used for subcutaneous, intranasal and oral immunization of experimental animals, and their immune response will be evaluated. A different group of animals will be similarly immunized with inactivated virus in solution for comparison. If a significant enhancement in the protective immune response is observed using microencapsulated PI3 virus antigens, more detailed studies will be subsequently pursued for development of a multivalent subunit vaccine using parainfluenza type 1, 2 and 3 envelope glycoproteins. Studies will also be conducted to understand the mechanism of protection (cellular/antibody mediated), and the duration of such response. Finally, microencapsulated virus envelope glycoproteins will be utilized for a clinical field trial for immunoprophylaxis against natural infection from parainfluenza viruses.